Biology subjects

Zhu, J.

Publications and source records attributed to Zhu, J..

At least 73 records · Page 4Linked to original sources

bioRxiv2026

Quercetin Promotes Adipose Thermogenesis and Metabolic Health

The activation of thermogenesis in brown adipose tissue (BAT) represents a pivotal target for ameliorating disorders of glucose and lipid metabolism. This study sought to elucidate the regulatory effects of quercetin on thermogenesis and glucose-lipid metabolism within brown adipocytes, alongside its underlying molecular mechanisms. The findings demonstrated that quercetin markedly upregulated the expression of uncoupling protein 1 (UCP1), a critical thermogenic protein in brown adipocytes, thereby enhancing cellular thermogenic capacity and effectively mitigating glucose and lipid metabolism disorders. Subsequent mechanistic investigations confirmed that quercetin activated the COX2-PGE2-EP4-UCP1 signaling axis by augmenting the stability of cyclooxygenase 2 (COX2) protein, thus mediating its thermogenic-promoting and metabolism-improving effects. This study identifies quercetin as a potential therapeutic agent for the improvement of glucose and lipid metabolism disorders, uncovers a novel molecular mechanism through which quercetin regulates brown adipocyte thermogenesis, and provides a theoretical and experimental foundation for the application of quercetin in the prevention and treatment of obesity and related metabolic diseases.

molecular biology↗

bioRxiv2026

Engineering a pacemaker-driven human mini-heart guided by spatial multi-omics of sinoatrial node development

The human sinoatrial node (SAN) functions as the primary pacemaker of the heart and coordinates the hierarchical electrical activity that drives cardiac contraction. However, experimental systems capable of reconstructing pacemaker-driven cardiac organization in human tissues remain limited. Here we integrate spatial multi-omics of the human fetal SAN with stem-cell engineering to generate pacemaker organoids ("Sinoids") and assemble them into a pacemaker-driven human mini-heart composed of sinoatrial, atrial and ventricular cardiac modules. High-resolution spatial transcriptomics and single-nucleus multi-omic analyses of human fetal SAN tissues identify regulatory pathways guiding pacemaker lineage specification, which we leverage to engineer human pluripotent stem cell-derived SAN organoids with robust pacemaker identity and electrophysiological activity. When integrated with atrial and ventricular cardioids, Sinoids initiate and coordinate electrical activation across assembled cardiac tissues, establishing directional propagation of electrophysiological signals within structured mini-heart organoids. Combining AI-guided perturbation modeling with functional validation further identifies conserved regulatory pathways controlling pacemaker specification and regionalization, including YAP-TEAD and NRG-ERBB signaling. Together, these results establish a multi-omic-guided strategy for engineering pacemaker tissues and reconstructing cardiac conduction hierarchy in vitro. The pacemaker-driven mini-heart platform provides a modular human cardiac system for studying pacemaker biology, modeling arrhythmia mechanisms and enabling electrophysiological drug discovery.

bioinformatics↗

bioRxiv2026

G4 Eurasian avian-like H1N1 swine influenza viruses exhibit enhanced pathogenicity potential in mice and pigs

Currently circulating swine influenza viruses (SIVs) mainly include H1N1, H1N2, and H3N2 subtypes. In this study, two G4 genotype Eurasian avian-like (EA) H1N1 SIVs were isolated from 556 samples collected between 2023 and 2026. A systematic analysis was conducted on the two EA H1N1 isolates (FYD30 and YZF69) to assess their pandemic potential. The hemagglutinin (HA) proteins of both H1N1 viruses possessed residues 225E and 228S, indicating enhanced affinity for human-like -2,6-linked sialic acid receptors, which was confirmed by receptor-binding assays. Polymerase activity tests demonstrated that the two SIVs exhibited significantly higher activity in mammalian cells, relative to avian cells, which is consistent with the efficient replication in mammalian cells. Challenge experiments revealed that both H1N1 caused significant pathogenicity in mice and pigs, with YZF69 exhibited higher virulence than FYD30. The higher virulence of YZF69 may be attributed to its molecular features, including the NP Q357K mutation, and an additional glycosylation site in HA. In conclusion, currently circulating EA H1N1 SIVs have acquired key molecular signatures of mammalian adaptation, exhibit enhanced virulence in mammals, and continue to undergo extensive reassortment driven by international swine trade. These findings highlight the potential pandemic risk of SIVs and underscore the urgent need for strengthened surveillance.

microbiology↗

bioRxiv2026

Bacteria rewire fungal antimicrobial gene expression in microbial arms races

Microbial communities are shaped by antagonistic interactions, yet how competitors evade antimicrobial strategies in a community context remains unclear. Fungi deploy antimicrobial proteins (AMPs) to suppress bacterial niche competitors, but how bacteria counteract these defences is unknown. Here we show that soil microbiota suppress fungal AMP expression, revealing a previously unrecognized mode of intermicrobial interference. In the soil-borne pathogen Verticillium dahliae, AMP genes are highly conserved yet broadly repressed in the presence of natural microbial communities. This repression extends across diverse fungi, suggesting a widespread phenomenon. Correlation analyses of AMP expression and community compositions linked the bacterial genera Leptothrix and Devosia to repression of the V. dahliae AMPs VdL1 and VdD1, respectively. Both AMPs antagonize these bacterial taxa, and microbiota-mediated repression of VdL1 reduces its contribution to fungal soil colonization. Together, our findings reveal that bacteria can evade fungal antagonism by suppressing AMP deployment, highlighting community-level control of microbial competition.

microbiology↗

bioRxiv2026

Microglial sTREM2 limits dyskinesia and acts on TrkB to support circuit plasticity

Microglia continuously survey the brain and shape neuronal activity, but their contribution to experience-dependent synaptic plasticity is unclear. Levodopa-induced dyskinesia (LID) is a disabling complication of late-stage Parkinsons disease (PD) that is linked to maladaptive striatal remodeling and is often assumed to reflect detrimental neuroinflammation. Here we identify a dyskinesia-associated microglial gene program in the striatum of PD patients and show that microglia instead act as a protective brake on LID. In a mouse model, microglial depletion exacerbated dyskinesia, whereas microglial repopulation mitigated it. Delivery of AAV expressing soluble TREM2 (sTREM2) similarly reduced LID without impairing the therapeutic benefit of levodopa. Single-nucleus transcriptomics revealed that microglial loss drives extensive remodeling of both direct and indirect spiny projection neurons (SPNs), while repopulation or sTREM2 reverses a large fraction of LID-associated transcriptional changes. Mechanistically, sTREM2 directly engages TrkB and potentiates BDNF-dependent TrkB-ERK signaling, consistent with positive allosteric modulation. Functionally, sTREM2 enhances BDNF-TrkB-dependent hippocampal synaptic plasticity and acutely rebalances striatal dendritic excitability in a compartment- and cell type-specific manner. These findings reveal an unexpected neuroimmune pathway in which microglia restrain maladaptive plasticity via sTREM2-TrkB signaling, with therapeutic implications.

neuroscience↗

bioRxiv2026

Encoded metabolic remodeling amplifies drug resistance in Mycobacterium tuberculosis

Antibiotic pressure causes pathogens to evolve many forms of altered drug susceptibility. In addition to target or activator mutations conferring canonical drug resistance, mutations can serve as steppingstones to or enhancers of resistance. In clinical strains of Mycobacterium tuberculosis (Mtb), we find that idsA2, which encodes an isoprenyl pyrophosphate synthase involved in the synthesis of precursors for essential components of the cell wall and electron transport chain, is undergoing diversifying selection and that these mutations are associated with the acquisition of first-line antibiotic resistance. By engineering isogenic Mtb strains that express clinically prevalent variants of idsA2, we show that clinical variants increase the minimum inhibitory concentration of ethambutol and, to a lesser extent, of isoniazid. Targeted lipid analyses reveal that disrupting IdsA2 function redirects limited resources in the isoprenoid synthesis pathway, leading to increased production of decaprenylphosporyl pentose which can compete with ethambutol for binding to arabinosyltransferases. IdsA2 mutations most often occur after embB mutation and lead to a multiplicative increase in ethambutol resistance. Thus, identification of idsA2 mutations can be utilized to improve the specificity of genotypic ethambutol susceptibility testing. Together, this work defines idsA2 as an ethambutol resistance gene and demonstrates how metabolic remodeling can augment drug resistance. Author SummaryTuberculosis is the deadliest infectious disease in the world and becomes more difficult to treat with the acquisition of drug resistance. Defining the mechanisms and genetic basis of drug resistance will allow for improved screening and drug regimen optimization for treatment success. To identify previously unrecognized mechanisms of altered drug susceptibility, we have combined population genomics and experimental genetics approaches, focusing on Mycobacterium tuberculosis genes evolving in clinical strains. We identified idsA2 as a target of frequent mutations that are associated with drug resistance. Experimental data indicate that idsA2 variants decrease the susceptibility of the bacteria to multiple antibiotics through isoprenoid synthesis remodeling, with the strongest effect on ethambutol resistance. IdsA2 mutations often occur after embB mutations to multiplicatively increase ethambutol resistance. These data suggest that inclusion of idsA2 variants in drug resistance testing could improve the specificity of genotypic detection of ethambutol resistance.

microbiology↗

bioRxiv2026

Resident and Engrafting E. coli Populations Expand Through Dissimilar Pathways in the Inflamed Gut

Intestinal inflammation increases the abundance of Enterobacteriaceae in the gastrointestinal tract by several orders of magnitude. These population expansions, or blooms, are associated with disease progression and have been suggested to exacerbate intestinal pathologies in some settings. Murine studies have shown that during the early stages of Escherichia coli colonization, i.e., during engraftment, inflammation enhances fitness through processes that depend on Moco, an enzyme cofactor found in a variety of oxidoreductases that consists of molybdenum coordinated by a pterin molecule. Using a murine commensal E. coli isolate and a DSS-induced colitis model in mice, we investigated whether Moco is also important for blooms of E. coli that are part of the resident microbiota, that is, for E. coli that have engrafted well before the onset of inflammation. We show that resident wild-type and Moco- E. coli exhibit comparable expansions in response to inflammation, indicating that, in this context, Moco-dependent processes such as nitrate respiration or formate oxidation were not important for inflammation-induced blooms. We find that Moco is important, however, for E. coli colonization in the absence of inflammation, suggesting that alternative respiratory pathways or other Moco-dependent processes are necessary for E. coli colonization of a healthy murine gut. Our findings demonstrate that the mechanisms underlying inflammation-induced blooms can depend on the temporal relationship between engraftment and inflammation, and also highlight the importance of considering colonization stage in identifying and interpreting the factors that affect the fitness of microbes colonizing the intestine.

microbiology↗

bioRxiv2026

Immunization With Herpes Simplex Virus Nanoparticles Targeting Both Attachment and Fusion Protect Against Infection

Herpes simplex virus 2 (HSV-2) is associated with genital ulcers, neonatal encephalitis, increased risk of HIV infection, and dementia. There is no licensed HSV-2 vaccine. We developed nanoparticles displaying the HSV-2 attachment protein gD and fusion mediation protein complex gH/gL. Immunization of mice and non-human primates elicited high levels of neutralizing antibodies. Vaccination conferred robust protection in mice, preventing disease and nearly eliminating infection and shedding following HSV-2 challenge. While gD induced high neutralizing antibody titers, gH/gL contributed substantially to protection despite lower neutralization titers. Instead, gH/gL immunization generated strong fusion-blocking responses which were an important correlate of protection, showing that standard neutralization assays incompletely capture the importance of fusion-blocking activity. These findings demonstrate that targeting both HSV-2 attachment and fusion elicit complementary mechanisms for protection from infection and that neutralizing antibody alone may be insufficient for protection. Overall, these results present an innovative strategy for an HSV-2 vaccine.

immunology↗

bioRxiv2026

CellChem: Cellular transcriptional responses reshape molecular representation space for efficient and multi-scale drug discovery

Despite decades of progress in computational drug discovery, deep learning-based molecular representation models remain largely structure-centric, assuming that chemical similarity approximates functional similarity. However, drug effects in cells are shaped not only by chemical similarity but also by molecular interactions in the cellular context. To capture this complexity, we introduce CellChem, a cellular-chemical representation-learning framework that learns cell-guided molecular representations of small-molecule actions within cells. By incorporating large-scale cellular transcriptional profiles during pretraining, CellChem reshapes molecular representation space from structure-centric to a balanced integration of structure and function. The learned CellChem molecular representations exhibit biologically meaningful geometric organization, such that distances between molecules encode not only structural similarity but also similarity in the cellular responses they elicit, independent of downstream tasks. Using downstream derivative models such as cell-guided compound-protein interaction prediction and drug-induced transcriptional response profile generation, CellChem supports highly efficient, multi-scale drug discovery, achieving significantly better performance than traditional models.

molecular biology↗

bioRxiv2026

Designer indicators for two-photon recording of subthreshold voltage dynamics

Subthreshold voltage dynamics are critical for neuronal information integration, yet they remain understudied in vivo due to the limitations of current tools. While genetically encoded voltage indicators (GEVIs) offer a promising alternative, their application for deep-tissue recording using two-photon (2P) microscopy--a preferred method for deep-tissue recording--has been hindered by insufficient sensitivity for detecting millivolt-scale subthreshold signals. Here, we refined our multiparametric two-photon high-throughput screening platform to develop two novel GEVIs, JEDI3sub and JEDI3hyp, tailored explicitly for subthreshold voltage detection. Through fast 2P optical recording in awake, behaving mice, we demonstrated the superior sensitivity of JEDI3 indicators compared to JEDI-2P. We also showed that JEDI3sub can track population-level subthreshold optical tuning, while JEDI3hyp reliably captured subthreshold dynamics associated with sharp-wave ripple oscillations in hippocampal PV interneurons. Finally, JEDI3hyp facilitated extended imaging of brain-state-dependent, millivolt-scale subthreshold voltage changes across deep-layer somas, fine dendritic structures, and diverse cell types. By addressing the critical gap in 2P optical recording of subthreshold voltage dynamics, JEDI3 indicators open new avenues for studying neural information processing and its alterations in health and disease.

neuroscience↗

bioRxiv2026

Sympathoadrenal Lineage Plasticity Drives Intratumoral Heterogeneity in Paraganglioma, Neuroblastoma and Composite Tumors Following KIF1Bb-NF1 Loss

Neuroblastoma (NB) and paraganglioma (PPGL) arise from the sympathoadrenal lineage, yet their developmental relationship and heterogeneity remain unclear. Single-cell and spatial transcriptomics revealed shared, spatially organized developmental states, including populations characteristic of the other tumor type, chromaffin-like cells in NB and neuroblast-like cells in PPGL and hybrids co-expressing adjacent states. Deconvolution of an independent PPGL cohort associated metastatic disease most strongly with chromaffin hybrid states, alongside connecting progenitor-like, cycling neuroblast, and early chromaffin identities, whereas non-metastatic tumors were enriched for differentiated late chromaffin identities. In mice, combined loss of the candidate 1p36 tumor suppressor KIF1B{beta} and NF1 recapitulates these developmental architectures by prolonging developmental plasticity, reactivating embryonic neurogenic programs, and driving chromaffin-to-neuroblast transitions generating pheochromocytoma, neuroblastoma and composite tumors. Mouse tumors contained discrete spatial domains of developmental and neoplastic states that mirrored those in human PPGL. Together, our findings establish chromaffin-neuroblast plasticity as a mechanism of sympathoadrenal tumor heterogeneity and identify hybrid developmental states as a potential indicator of plasticity associated with metastatic PPGL.

cancer biology↗

bioRxiv2026

A versatile, positive-going voltage indicator that enables accessible two-photon recordings in vivo

Genetically encoded voltage indicators (GEVIs) enable cell-type-specific optical readout of membrane potential, but two-photon (2P) spike detection has been hampered by low signal-to-noise and ultrafast off-kinetics, restricting use to specialized microscopes. We introduce FORCE1s, a green, positive-going GEVI engineered to make robust 2P voltage imaging broadly accessible. FORCE1s brightens from a dark baseline during depolarization, reports spikes with [~]100% {Delta}F/F in awake mice, and displays repolarization kinetics that are tuned for reliable spike detection at sub-kilohertz frame rates. As a result, FORCE1s supports spike-resolved multi-cell recordings on standard resonant-scanning microscopes, and further scales to larger fields of view and neuron counts on advanced modalities. FORCE1s also enables multiplexed voltage-neurotransmitter imaging and extended recordings in freely moving mice using a compact, affordable MEMS-based 2P miniscope. Together, these advances establish FORCE1s as a community-ready tool that democratizes deep-tissue voltage imaging across platforms and experimental contexts.

neuroscience↗

bioRxiv2026

CA19-9 promotes liver metastasis of pancreatic cancer through E-selectin mediated extravasation

Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes to the liver, which drives patient mortality. CA19-9 is elevated in most PDAC tumors and is widely used as a clinical biomarker. Elevated serum levels are associated with poor outcomes. However, whether CA19-9 functionally contributes to metastatic progression has not been fully defined, in part because mice lack endogenous CA19-9 expression. Here, using syngeneic murine PDAC cells engineered to express CA19-9, we investigated its functional role in liver metastasis. In splenic injection models, CA19-9 expression markedly increased liver metastatic burden by promoting both metastatic seeding and subsequent metastatic outgrowth. In vitro, CA19-9 enhanced tumor cell adhesion to endothelial cells through interaction with E-selectin. Metastatic seeding of CA19-9-expressing cells was reduced by genetic deletion of E-selectin or antibody neutralization of either CA19-9 or E-selectin in vivo. Therapeutic targeting of CA19-9 with a neutralizing antibody markedly reduced liver metastatic burden after metastatic seeding. CA19-9 expression increased AKT signaling in PDAC cells and liver metastases, and CA19-9 levels correlated with AKT activation in human PDAC tissues. These findings show that CA19-9 promotes PDAC liver metastasis through E-selectin-dependent metastatic seeding and AKT-associated metastatic outgrowth, highlighting CA19-9 as a functional mediator of PDAC metastasis and a potential therapeutic target.

cancer biology↗

bioRxiv2026

Levosimendan inhibits HIV-1 infection in myeloid cells in the RIOK1-dependent manner

Despite of the highly potent antiretroviral therapies, HIV-1 establishes persistent infection and causes chronic inflammation in AIDS patients. Beyond CD4+ T cells, HIV-1 infects myeloid cells, including circulating monocytes and tissue-resident macrophages, and integrates with host genomes to form stable viral reservoirs. To achieve a functional HIV cure, latency-promoting agents (LPAs) have been developed for the "block-and-lock" strategy to reinforce deep HIV-1 latency and permanently silence proviruses. However, most LPAs have been tested mainly in CD4+ T cells, and their efficacy in myeloid cells remains unclear. In this study, we reported that levosimendan (LSM), a drug approved for clinic use to treat heart failures, is able to inhibit HIV lytic infection and reactivation in myeloid cells. LSM blocked viral lytic reactivation in HIV-1 latently infected monocytic cells (TH89GFP, U1) and microglial cells (HC69). LSM also inhibited HIV infection in human induced pluripotent stem cell (iPSC) derived microglia (iMG), primary human resident liver macrophages (Kupffer cells) as well as human monocyte-derived macrophages (MDMs). Furthermore, we demonstrated that overexpression of a predicted drug target of LSM, the conserved serine/threonine kinase RIOK1 (RIO kinase 1), overcomes LSMs anti-HIV effect. Overall, our studies concluded that LSM is a promising LPA to inhibit HIV-1 infection in myeloid cells in the RIOK1-dependent manner.

microbiology↗

bioRxiv2026

METTL14-dependent m6A modification restrains interferon signaling to prevent myocarditis and dilated Cardiomyopathy

The impact of inflammation on heart failure is increasingly recognized; but how cardiomyocyte restrains innate immune activation remains poorly defined, and nor does the role of N-methyladenosine (mA) modification in maintaining cardiac immune homeostasis. Here, we demonstrate that cardiomyocyte-specific deletion of the mA methyltransferase METTL14 triggers myocarditis, dilated cardiomyopathy, and premature lethality. Meanwhile, widespread hypomethylation and upregulation of innate immune and necroptosis-related transcripts in Mettl14-deficient hearts exemplified by IFN-1 and STAT1. Mechanistically, METTL14 deficiency promotes RIPK1 accumulation thereby priming cardiomyocytes for necroptosis and inflammatory cell death. Genetic ablation of IFN-I receptor Ifnar1 can largely rescue the processes and improve cardiac function and survival. Furthermore, METTL14 loss disrupts mitochondrial integrity and autophagy/mitophagy flux, suggesting mitochondrial dysfunction-driven innate immune activation upstream of IFN-I signaling. Collectively, these findings identify METTL14-mediated mA modification as a critical safeguard against cardiomyocyte-intrinsic IFN-I signaling and necroptosis and establish an epitranscriptomic-innate immune axis that drives inflammatory heart failure.

pathology↗

bioRxiv2026

Spatial organization of plant defense at the infection front

Plants lack specialized immune cells and instead rely on coordinated cellular responses to restrict pathogen invasion while preserving tissue integrity. How plant immunity spatially organizes these responses remains unclear. Using live-cell reporters in Arabidopsis infected with Pseudomonas syringae, we show that effector-triggered immunity, superimposed on pattern-triggered immunity, establishes a sustained yet spatially confined immune architecture at the infection front. Defense activation persists for days but remains restricted to a narrow ring of cells surrounding viable bacterial microcolonies. Over time, immune activity spreads to adjacent layers, forming a coordinated, multilayered defense zone. This zonation extends beyond transcriptional activation to polarized callose deposition at pathogen-facing cell walls, reinforcing a localized containment boundary that limits pathogen spread. Consistent with previous single-reporter studies, simultaneous visualization of salicylic acid (SA) and jasmonic acid (JA) biosynthesis and response markers reveals a radial hormone gradient, with SA-enriched cells proximal to bacterial colonies and JA-enriched cells in surrounding regions. Individual cells predominantly activate one pathway, indicating that SA-JA antagonism is resolved through spatial compartmentalization across neighboring cells. Together, these findings establish immune zonation as a strategy for robust pathogen containment while minimizing collateral tissue damage. Significance statementPlants lack specialized immune cells and must coordinate defense responses across tissues to contain infection. Although plant immune responses are known to be locally activated, how they are organized across cells to form a stable containment boundary has remained unclear. Using live imaging of fluorescent bacterial microcolonies, we show that plant immunity forms a spatially organized defense zone surrounding viable infection sites. Within this zone, distinct defense activities are arranged in a radial gradient, with salicylic acid-associated responses enriched in cells near the pathogen and jasmonic acid-associated responses in surrounding cells. Rather than being resolved solely within individual cells, antagonistic hormone pathways are separated across neighboring cells. This spatial organization reveals immune zonation as a strategy for confining pathogen spread while preserving tissue integrity.

plant biology↗

bioRxiv2026

Trajectories of Response Inhibition Development in Adolescence

Adolescence is a pivotal developmental period during which cognitive control and the ability to suppress maladaptive impulses undergo profound refinement. Despite extensive behavioral and imaging studies in humans, the neural circuit mechanisms that drive the maturation of inhibitory control remain poorly understood. To address this gap, we performed a longitudinal multimodal study in macaque monkeys spanning the transition from puberty to adulthood, combining behavioral measurements, prefrontal neurophysiology, and structural neuroimaging within the same individuals. Behavioral performance in multiple variants of the antisaccade task improved dramatically across adolescence. In parallel, prefrontal cortical neurons exhibited robust developmental increases in task-related firing, particularly around the generation of goal-directed saccades, indicating maturation of neural representations supporting inhibitory control. Strikingly, trajectories of behavioral improvement and neural activity maturation were tightly predicted by the development of long-range white matter pathways linking frontal cortex with distributed brain networks. These findings identify white matter development as a key systems-level mechanism underlying the emergence of mature inhibitory control and prefrontal neural dynamics and establish a primate framework for understanding developmental vulnerabilities associated with neuropsychiatric disorders that emerge in adolescence and early adulthood.

neuroscience↗

bioRxiv2026

Dynamic cortical routing mediates temporal attention

Selecting information from dynamic streams requires mechanisms that prioritize a visual stimulus at a specific moment over preceding and subsequent stimuli at the same location. Whereas selective temporal attention has been found to enhance neural responses to stimuli, its impact on communication between brain regions remains unexplored. Here, we investigated whether prioritizing a stimulus at a specific time is achieved through selective routing of stimulus information across cortical networks using MEG. We developed a dynamic informational connectivity approach to quantify shared stimulus information between each region and the rest of the network. When stimuli compete in time, we found that temporal attention modulated the network at both early and late post-target time windows, routing information along two possible pathways--occipito-fronto-cingulate and occipito-temporal--via both transient bursts of network communication and theta-rhythmic replay. These results provide evidence that under dynamic sensory input, the timing of neural communication determines stimulus selection.

neuroscience↗